Mouse-Human Chimera Expresses Human Immune Responses

Researchers have created a human mouse chimera as a model system that is capable of expressing normal human immune responses to human pathogens that do not infect mice.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) transplanted autologous human hematopoietic fetal liver CD34+ cells into immune-deficient non-obese diabetic (NOD)/severe combined immune deficiency (SCID) mice previously implanted with human fetal thymic and liver tissues. The resulting chimeras, known as BLT (bone marrow liver thymic) mice, developed aspects of the human immune system and displayed high human T cell and other cell counts in virtually all of their tissues.

The BLT mice were challenged with either Epstein-Barr virus or toxic shock super antigen. Results of the study published in the October 22, 2006, online edition of Nature Medicine revealed that T cells in these mice generated human major histocompatibility complex class I– and class II–restricted adaptive immune responses to Epstein-Barr virus infection. Administration of the super antigen toxic-shock syndrome toxin 1 (TSST-1) resulted in the specific systemic expansion of human V-beta 2+ T cells, release of human pro-inflammatory cytokines, and localized, specific activation and maturation of human CD11c+ dendritic cells.

"The fact that virtually all human immune cells are adequately distributed in all the different mouse tissues has resulted in what is probably the most human-like immune system ever developed in mice,” said senior author Dr. J. Victor Garcia, professor of internal medicine at the University of Texas Southwestern Medical Center. "These human-mice chimeras are susceptible to a variety of human-specific viruses that could not be easily studied in the past, giving scientists a new way to study, develop, and implement novel vaccines and therapeutics to fight human diseases like cancer and AIDS.”



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University of Texas Southwestern Medical Center